PDBsum entry 1gq6

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protein metals Protein-protein interface(s) links
Hydrolase PDB id
Protein chains
295 a.a. *
_MN ×6
Waters ×572
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Proclavaminate amidino hydrolase from streptomyces clavuligerus
Structure: Proclavaminate amidino hydrolase. Chain: a, b, c. Synonym: proclavaminate amidino hydrolase ureohydrolase. Engineered: yes
Source: Streptomyces clavuligerus. Organism_taxid: 1901. Atcc: 27064. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Biol. unit: Hexamer (from PDB file)
1.75Å     R-factor:   0.142     R-free:   0.170
Authors: J.M.Elkins,I.J.Clifton,H.Hernandez,C.V.Robinson,C.J.Schofiel K.S.Hewitson
Key ref: J.M.Elkins et al. (2002). Oligomeric structure of proclavaminic acid amidino hydrolase: evolution of a hydrolytic enzyme in clavulanic acid biosynthesis. Biochem J, 366, 423-434. PubMed id: 12020346 DOI: 10.1042/BJ20020125
20-Nov-01     Release date:   06-Jun-02    
Go to PROCHECK summary

Protein chains
P0DJQ3  (PAH_STRCL) -  Proclavaminate amidinohydrolase
313 a.a.
295 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Proclavaminate amidinohydrolase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Clavulanate Biosynthesis
      Reaction: Amidinoproclavaminate + H2O = proclavaminate + urea
+ H(2)O
= proclavaminate
+ urea
      Cofactor: Mn(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     clavulanic acid biosynthetic process   1 term 
  Biochemical function     hydrolase activity     4 terms  


DOI no: 10.1042/BJ20020125 Biochem J 366:423-434 (2002)
PubMed id: 12020346  
Oligomeric structure of proclavaminic acid amidino hydrolase: evolution of a hydrolytic enzyme in clavulanic acid biosynthesis.
J.M.Elkins, I.J.Clifton, H.Hernández, L.X.Doan, C.V.Robinson, C.J.Schofield, K.S.Hewitson.
During biosynthesis of the clinically used beta-lactamase inhibitor clavulanic acid, one of the three steps catalysed by clavaminic acid synthase is separated from the other two by a step catalysed by proclavaminic acid amidino hydrolase (PAH), in which the guanidino group of an intermediate is hydrolysed to give proclavaminic acid and urea. PAH shows considerable sequence homology with the primary metabolic arginases, which hydrolyse arginine to ornithine and urea, but does not accept arginine as a substrate. Like other members of the bacterial sub-family of arginases, PAH is hexameric in solution and requires Mn2+ ions for activity. Other metal ions, including Co2+, can substitute for Mn2+. Two new substrates for PAH were identified, N-acetyl-(L)-arginine and (3R)-hydroxy-N-acetyl-(L)-arginine. Crystal structures of PAH from Streptomyces clavuligerus (at 1.75 A and 2.45 A resolution, where 1 A=0.1 nm) imply how it binds beta-lactams rather than the amino acid substrate of the arginases from which it evolved. The structures also suggest how PAH selects for a particular alcohol intermediate in the clavam biosynthesis pathway. As observed for the arginases, each PAH monomer consists of a core of beta-strands surrounded by alpha-helices, and its active site contains a di-Mn2+ centre with a bridging water molecule responsible for hydrolytic attack on to the guanidino group of the substrate. Comparison of structures obtained under different conditions reveals different conformations of a flexible loop, which must move to allow substrate binding.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20711575 J.Y.Song, S.E.Jensen, and K.J.Lee (2010).
Clavulanic acid biosynthesis and genetic manipulation for its overproduction.
  Appl Microbiol Biotechnol, 88, 659-669.  
19093830 E.Y.Shishova, L.Di Costanzo, F.A.Emig, D.E.Ash, and D.W.Christianson (2009).
Probing the specificity determinants of amino acid recognition by arginase.
  Biochemistry, 48, 121-131.
PDB codes: 3e6k 3e6v 3e8q 3e8z 3e9b
17406634 H.Hernández, and C.V.Robinson (2007).
Determining the stoichiometry and interactions of macromolecular assemblies from mass spectrometry.
  Nat Protoc, 2, 715-726.  
17328674 M.Sharon, and C.V.Robinson (2007).
The role of mass spectrometry in structure elucidation of dynamic protein complexes.
  Annu Rev Biochem, 76, 167-193.  
16251194 H.Arulanantham, N.J.Kershaw, K.S.Hewitson, C.E.Hughes, J.E.Thirkettle, and C.J.Schofield (2006).
ORF17 from the clavulanic acid biosynthesis gene cluster catalyzes the ATP-dependent formation of N-glycyl-clavaminic acid.
  J Biol Chem, 281, 279-287.  
16113715 N.J.Kershaw, M.E.Caines, M.C.Sleeman, and C.J.Schofield (2005).
The enzymology of clavam and carbapenem biosynthesis.
  Chem Commun (Camb), (), 4251-4263.  
15355972 H.J.Ahn, K.H.Kim, J.Lee, J.Y.Ha, H.H.Lee, D.Kim, H.J.Yoon, A.R.Kwon, and S.W.Suh (2004).
Crystal structure of agmatinase reveals structural conservation and inhibition mechanism of the ureohydrolase superfamily.
  J Biol Chem, 279, 50505-50513.
PDB codes: 1wog 1woh 1woi
15342599 K.Tahlan, C.Anders, and S.E.Jensen (2004).
The paralogous pairs of genes involved in clavulanic acid and clavam metabolite biosynthesis are differently regulated in Streptomyces clavuligerus.
  J Bacteriol, 186, 6286-6297.  
14623876 M.E.Caines, J.M.Elkins, K.S.Hewitson, and C.J.Schofield (2004).
Crystal structure and mechanistic implications of N2-(2-carboxyethyl)arginine synthase, the first enzyme in the clavulanic acid biosynthesis pathway.
  J Biol Chem, 279, 5685-5692.
PDB codes: 1upa 1upb 1upc
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